Association between pregnancy losses in women and risk of atherosclerotic disease in their relatives: a nationwide cohort study

Mattis Flyvholm Ranthe; Lars Jorge Diaz; Ida Behrens; Henning Bundgaard; Jacob Simonsen; Mads Melbye; Heather Allison Boyd

doi:10.1093/eurheartj/ehv549

Association between pregnancy losses in women and risk of atherosclerotic disease in their relatives: a nationwide cohort study

Mattis Flyvholm Ranthe, Lars Jorge Diaz, Ida Behrens, Henning Bundgaard, Jacob Simonsen, Mads Melbye, Heather Allison Boyd

Department of Clinical Medicine

5 Citations (Scopus)

Abstract

AIMS: A common underlying mechanism with a genetic component could link pregnancy losses with vascular disease. We examined whether pregnancy losses (miscarriages and stillbirths) and atherosclerotic outcomes co-aggregated in families.

METHODS AND RESULTS: Using Danish registers, we identified women with pregnancies in 1977-2008, and their parents (>1 million) and brothers (>435 000). We followed parents for incident ischaemic heart disease (IHD), myocardial infarction (MI), and cerebrovascular infarction (CVI), and brothers for a broader combined atherosclerotic endpoint. Using Cox regression, we estimated hazard ratios (HRs) for each outcome by history of pregnancy loss in daughters/sisters. Overall, parents whose daughters had 1, 2, and ≥3 miscarriages had 1.01 [95% confidence interval (CI) 0.99-1.04], 1.07 (95% CI 1.02-1.11), and 1.10 (95% CI 1.02-1.19) times the rate of MI, respectively, as parents whose daughters had no miscarriages. For parents with ≥3 daughters, the HRs were 1.12 (95% CI 1.02-1.24), 1.29 (95% CI 1.13-1.48), and 1.33 (95% CI 1.12-1.57). Effect magnitudes did not differ for fathers and mothers. We observed similar patterns for IHD and CVI (parents) and the atherosclerotic endpoint (brothers). Parents whose daughters had stillbirths had 1.14 (95% CI 1.05-1.24) and 1.07 (95% CI 0.96-1.18) times the rates of MI and CVI, respectively, as parents whose daughters had no stillbirths.

CONCLUSION: Certain pregnancy losses and atherosclerotic diseases in both heart and brain may have a common aetiologic mechanism. Women in families with atherosclerotic disease may be predisposed to pregnancy loss; conversely, pregnancy losses in first-degree relatives may have implications for atherosclerotic disease risk.

Original language	English
Journal	European Heart Journal
Volume	37
Issue number	11
Pages (from-to)	900-7
Number of pages	8
ISSN	0195-668X
DOIs	https://doi.org/10.1093/eurheartj/ehv549
Publication status	Published - 14 Mar 2016

Keywords

Journal Article
Research Support, Non-U.S. Gov't

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title = "Association between pregnancy losses in women and risk of atherosclerotic disease in their relatives: a nationwide cohort study",

abstract = "AIMS: A common underlying mechanism with a genetic component could link pregnancy losses with vascular disease. We examined whether pregnancy losses (miscarriages and stillbirths) and atherosclerotic outcomes co-aggregated in families.METHODS AND RESULTS: Using Danish registers, we identified women with pregnancies in 1977-2008, and their parents (>1 million) and brothers (>435 000). We followed parents for incident ischaemic heart disease (IHD), myocardial infarction (MI), and cerebrovascular infarction (CVI), and brothers for a broader combined atherosclerotic endpoint. Using Cox regression, we estimated hazard ratios (HRs) for each outcome by history of pregnancy loss in daughters/sisters. Overall, parents whose daughters had 1, 2, and ≥3 miscarriages had 1.01 [95% confidence interval (CI) 0.99-1.04], 1.07 (95% CI 1.02-1.11), and 1.10 (95% CI 1.02-1.19) times the rate of MI, respectively, as parents whose daughters had no miscarriages. For parents with ≥3 daughters, the HRs were 1.12 (95% CI 1.02-1.24), 1.29 (95% CI 1.13-1.48), and 1.33 (95% CI 1.12-1.57). Effect magnitudes did not differ for fathers and mothers. We observed similar patterns for IHD and CVI (parents) and the atherosclerotic endpoint (brothers). Parents whose daughters had stillbirths had 1.14 (95% CI 1.05-1.24) and 1.07 (95% CI 0.96-1.18) times the rates of MI and CVI, respectively, as parents whose daughters had no stillbirths.CONCLUSION: Certain pregnancy losses and atherosclerotic diseases in both heart and brain may have a common aetiologic mechanism. Women in families with atherosclerotic disease may be predisposed to pregnancy loss; conversely, pregnancy losses in first-degree relatives may have implications for atherosclerotic disease risk.",

keywords = "Journal Article, Research Support, Non-U.S. Gov't",

author = "Ranthe, {Mattis Flyvholm} and Diaz, {Lars Jorge} and Ida Behrens and Henning Bundgaard and Jacob Simonsen and Mads Melbye and Boyd, {Heather Allison}",

year = "2016",

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doi = "10.1093/eurheartj/ehv549",

language = "English",

volume = "37",

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T1 - Association between pregnancy losses in women and risk of atherosclerotic disease in their relatives

T2 - a nationwide cohort study

AU - Ranthe, Mattis Flyvholm

AU - Diaz, Lars Jorge

AU - Behrens, Ida

AU - Bundgaard, Henning

AU - Simonsen, Jacob

AU - Melbye, Mads

AU - Boyd, Heather Allison

PY - 2016/3/14

Y1 - 2016/3/14

N2 - AIMS: A common underlying mechanism with a genetic component could link pregnancy losses with vascular disease. We examined whether pregnancy losses (miscarriages and stillbirths) and atherosclerotic outcomes co-aggregated in families.METHODS AND RESULTS: Using Danish registers, we identified women with pregnancies in 1977-2008, and their parents (>1 million) and brothers (>435 000). We followed parents for incident ischaemic heart disease (IHD), myocardial infarction (MI), and cerebrovascular infarction (CVI), and brothers for a broader combined atherosclerotic endpoint. Using Cox regression, we estimated hazard ratios (HRs) for each outcome by history of pregnancy loss in daughters/sisters. Overall, parents whose daughters had 1, 2, and ≥3 miscarriages had 1.01 [95% confidence interval (CI) 0.99-1.04], 1.07 (95% CI 1.02-1.11), and 1.10 (95% CI 1.02-1.19) times the rate of MI, respectively, as parents whose daughters had no miscarriages. For parents with ≥3 daughters, the HRs were 1.12 (95% CI 1.02-1.24), 1.29 (95% CI 1.13-1.48), and 1.33 (95% CI 1.12-1.57). Effect magnitudes did not differ for fathers and mothers. We observed similar patterns for IHD and CVI (parents) and the atherosclerotic endpoint (brothers). Parents whose daughters had stillbirths had 1.14 (95% CI 1.05-1.24) and 1.07 (95% CI 0.96-1.18) times the rates of MI and CVI, respectively, as parents whose daughters had no stillbirths.CONCLUSION: Certain pregnancy losses and atherosclerotic diseases in both heart and brain may have a common aetiologic mechanism. Women in families with atherosclerotic disease may be predisposed to pregnancy loss; conversely, pregnancy losses in first-degree relatives may have implications for atherosclerotic disease risk.

AB - AIMS: A common underlying mechanism with a genetic component could link pregnancy losses with vascular disease. We examined whether pregnancy losses (miscarriages and stillbirths) and atherosclerotic outcomes co-aggregated in families.METHODS AND RESULTS: Using Danish registers, we identified women with pregnancies in 1977-2008, and their parents (>1 million) and brothers (>435 000). We followed parents for incident ischaemic heart disease (IHD), myocardial infarction (MI), and cerebrovascular infarction (CVI), and brothers for a broader combined atherosclerotic endpoint. Using Cox regression, we estimated hazard ratios (HRs) for each outcome by history of pregnancy loss in daughters/sisters. Overall, parents whose daughters had 1, 2, and ≥3 miscarriages had 1.01 [95% confidence interval (CI) 0.99-1.04], 1.07 (95% CI 1.02-1.11), and 1.10 (95% CI 1.02-1.19) times the rate of MI, respectively, as parents whose daughters had no miscarriages. For parents with ≥3 daughters, the HRs were 1.12 (95% CI 1.02-1.24), 1.29 (95% CI 1.13-1.48), and 1.33 (95% CI 1.12-1.57). Effect magnitudes did not differ for fathers and mothers. We observed similar patterns for IHD and CVI (parents) and the atherosclerotic endpoint (brothers). Parents whose daughters had stillbirths had 1.14 (95% CI 1.05-1.24) and 1.07 (95% CI 0.96-1.18) times the rates of MI and CVI, respectively, as parents whose daughters had no stillbirths.CONCLUSION: Certain pregnancy losses and atherosclerotic diseases in both heart and brain may have a common aetiologic mechanism. Women in families with atherosclerotic disease may be predisposed to pregnancy loss; conversely, pregnancy losses in first-degree relatives may have implications for atherosclerotic disease risk.

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1093/eurheartj/ehv549

DO - 10.1093/eurheartj/ehv549

M3 - Journal article

C2 - 26497162

SN - 0195-668X

VL - 37

SP - 900

EP - 907

JO - European Heart Journal

JF - European Heart Journal

IS - 11

ER -

Association between pregnancy losses in women and risk of atherosclerotic disease in their relatives: a nationwide cohort study

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